The essentiality of dietary omega-3 fatty acids remains an unresolved issue in human nutrition. The high content of docosahexaenoic acid (22:6omega3 or DHA) in the phospholipids of the retina and cerebral cortex suggests an important role in photoreceptor and neuronal membrane functions. We are investigating the effects of omega-3 fatty acid deprivation in rhesus monkeys during prenatal and postnatal development. DHA levels in retinal and brain phospholipids were greatly reduced, visual acuity development was delayed, retinal function as measured with the electroretinogram (ERG) was abnormal, and several behavioral changes have been identified. Effects on the ERG were not reversible by refeeding with fish oil or pure DHA at 10 months or older. We propose to complete two studies which are now in progress to address several remaining critical questions about the effects of dietary omega-3 fatty acid deficiency and supplementation: 1. What form of dietary omega-3 fatty acids is optimal for functional development? Should infants receive preformed DHA, arachidonic acid and the other very-long-chain essential fatty acids present in human milk? We are comparing several aspects of development in rhesus infants receiving a standard formula providing linolenic acid and in those receiving a formula with fatty acid composition simulating primate milk. 2. Can effects of low dietary omega-3 fatty acids be separated from those of high omega-6 fatty acids? In the current studies, omega-3 fatty acid deficient diets are matched to control diets in their level of omega-6 fatty acids. 3. Does omega-3 fatty acid deficiency affect other aspects of sensory function, and does it affect complex behaviors and cognitive abilities? We have new evidence for effects on behavioral reactivity and infant visual information processing, and we are exploring several other aspects of behavior and cognitive function in both infants and adults. 4. How do deficiency and supplementation alter phospholipid molecular species composition as well as the fatty acid composition of the retina, cerebral cortex and other tissues? Are there changes in the density and morphology of synapses in the cerebral cortex or in levels of key neurotransmitters and their receptors? These studies will help to determine nutritional needs for omega-3 fatty acids during development, and the results will have important implications for the composition of human infant formulas as well as for the optimum diets of pregnant and lactating women. These studies will also help to define the roles of these fatty acids in neural, sensory and behavioral development.